JPH0314513A - Rinse composition in mouth - Google Patents

Abstract

PURPOSE: To prepare a stable oral rinse composition comprising a benzophenanthridine alkaloid and a specific buffer system. CONSTITUTION: This oral rinse composition comprises one or more benzophenanthridine alkaloids (e.g. sanguinarine or chelerythrine) and a buffer system in an amount sufficient to regulate the pH of the composition to 4.0-5.6 (e.g. sodium citrate and citric acid or sodium acetate and citric acid) and, as necessary, a zinc salt and is prepared by suitably formulating water, ethyl alcohol, a humectarnt, a surfactant, a sweetener, a perfume, a colorant, etc., as other ingredients therewith. The benzophenanthridine alkaloids are contained in an amount of 0.01-0.2wt.% in an aqueous solution. The composition is an oral rinse, comprising a new sanguinaria extract, having excellent stability, improved in both uptake of the sanguinaria into dental plaques and prevention of acid production with salivary bacteria.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention is directed to the treatment of Sanguinaria (saBuina) to plaque.
ria) and improves the ability to prevent acid production by salivary bacteria after glucose exposure.
Concerning a new Sanguina Rinlo internal rinse stabilized with <Prior art> Sanguinarine nadensis
Canadensis) is Blood Ru} (Bl
oodroot. )． Pucoon
It is known as Touerwart and is derived from a North American grass. This plant and its sap have been used for various purposes in prehistoric as well as posthistoric times. It has been used as a natural and historical folk medicine.

The plant was generally used either undried (fresh) or dried whole. The usual formulation involves powdering the dried plant and mixing it with a carrier. This folk remedy has been tried for asthma, bronchitis, dysentery, emphysema, and other ailments. Sanguinarine, cheleritine and other penzophenanthridine alkaloids are known alkaloids of the isoquinoline family. Plant sources of these alkaloids include papaveraceae, Fumariaceae and Rutaceae.
Recovery of the alkaloids from various species such as ULaceae) is disclosed in Yoneda Patent No. 4,145,412.
No.: 4,517,172; 4,590
．． No. 061: Same No. 4. 599. No. 228: Same No. 4, 683. No. 133: Same No. 4,689,21
No. 6: No. 4,767,861 and No. 4, 76
9. It is described in No. 452. The production of these alkaloids by plant tissue culture is
Report Ls (198g) 7:410-413.

The use of an extract containing benzophenant.hridine alkaloids as part of a mouth cleansing preparation without using known chromatographic methods is described in the aforementioned US patent.

The use of a benzophenanthridine alkaloid-containing extract of Sanguinaria canadensis as a component of a mouth cleansing preparation is also disclosed in the Fuki Yoneda patent. The use of Sanguinaria canadensis L. extracts is described in U.S. Pat. Nos. 4,517,172 and 4. 5
Braak disk rose (disclo) in issue 90061
ziB) agent.

Mouth rinses and toothpastes containing Sanguinaria extracts are known to be effective anti-blanch and anti-gingivitis agents, and are also effective against oral malodor and tartar.

Old U.S. Patent No. 209,331 and U.S. Patent No. 2,3
No. 44,830 describes the use of Sanguinaria in combination with zinc chloride. Although there is no mention that zinc chloride is required to maintain efficacy, Sanguinaria extracts are typically used in dentifrices in combination with zinc chloride or other metal salts such as tin chloride. (U.S. Patent Nos. 4 and 6
No. 89.216> When combining Sanguinaria extract with zinc chloride in a mouth rinse vehicle, pi is usually adjusted to 3. The prior art teaches adjusting zinc mouth rinses to a pH of 3 to prevent the formation of insoluble zinc compounds such as zinc hydroxide and zinc oxychloride. US Patent 4,
See No. 289,755. Additionally, the Sanguinaria solution is acidified to prevent the presence of pseudobasic form B of the penzophenanthridine alkaloid present during the extraction. The pseudobasic forms of alkaloids present in the extract become viable at about pH 5.6.

(Jones et a1,) J. of
Natural ProducLs, Vol. 4
9, No. 6, PP-1109-1111. 1986
(November-December 2016).

Additionally, the extract was adjusted to pH 3 to maintain the chemical stability of the extract and prevent the formation of brown to black precipitates.

This precipitation is believed to be due to the condensation of tannins and the presence of lignin-like substances within the extract. PH3.4
A 1% solution of Sanguinaria extract filtered with
The pH needs to be acidic (pH=3>). Zinc-containing rinses are generally formulated in pll3 for stabilizing purposes, as described in U.S. Pat. No. 4,289,755. Others patent teaches that even higher pHs can be achieved through the use of glycine. U.S. Pat.
Please see No. 339,432. Low pH rinses, especially those containing zinc chloride, also have a sour taste. (Problem to be Solved by the Invention) The present invention uses a specific buffer system and an emulsifier with improved chemical compatibility with the extract.
The present invention provides a mouth rinse containing a novel Sanguinaria extract with excellent stability, improved uptake of Sanguinaria into braques, and improved prevention of acid production by salivary bacteria. It has also been found that impurities in the emulsifier can be detrimental to the stability of the extract. pH4.
It was also found that using the No. 5 rinse could significantly reduce malodor over an 8-hour period compared to a placebo rinse. <Means for Solving the Problems> The mouth rinse composition of the present invention is aqueous.

The composition contains one or more penzophenanthridine alkaloids and, if desired, also one or more zinc salts, such as zinc chloride. Penzophenanthridine alkaloids useful in the compositions of the invention include sanguinarine (sang
uinarine), chelerythrine (cheeryth
rine), Sangilchin (saBuilt.in)
e), cheliluLine, cheliluline, and sanguirubine. It has also been found that the formation of precipitates in oral compositions containing benzophenanthridine alkaloids and subsalt salts can be prevented by using a buffer system. A pH-stable, non-precipitate-forming composition comprising a zinc salt is provided by the present invention.

Other useful zinc salts include, for example, zinc acetate, zinc gluconate, zinc sulfate, zinc salicylate, zinc tartrate,
Included are zinc L-acid, zinc phenolsulfone and zinc carboxymethyloxysuccinate. Water-soluble zinc salts are preferred in the amount present in the composition, but water-insoluble salts can also be used provided they are properly suspended or emulsified.

See, for example, the zinc salts described in US Pat. No. 4,100,269.

The amount of zinc salt present can vary up to about 0.5% by weight, preferably from about 0.05 to 0.25% by weight.

The mouth rinse composition of the present invention comprises, in addition to the benzophenanthridine alkaloid, about 50 to 95 weight percent water (preferably about 75 to 90 percent); 5 to 25 weight percent ethyl alcohol (preferably about 5 to 25 weight percent); 15%): 2-15% by weight of glycerin or other suitable wetting agent; 0.1-3.0% surfactant (emulsifier); 0.0% sweetener.
2 to 1.0% by weight: fragrance 0.05 to 0.4% by weight:
and colorant O to 0.01% by weight.

Pond wetting agents suitable for this application include sorbitol, mannitol, propylene glycol, polyethylene glycol, used individually or in combination. The function of this humectant is as a texture, texture and flavor modifier and as a solubilizer.

Types of surfactants suitable for this application include:

Anions such as sodium lauryl sulfonate, sodium lauryl succinate and sodium dodecyl sulfonate. Nonions, such as polyethylene sorbitan fatty acid esters, such as sorbitan isostearate, polysorbate 20, polysorbate 60, polysorbate 80 and amine oxides, such as cocoa amine oxide, amphoteric, such as cocoampholytic lupoxybrobionate and alkyl betaines, such as cocoa amide. betaine.

The surfactants may be used individually or in combination.

Types of sweeteners suitable for this application include asbertame (a
spertame), acesulfem (acesul)
fame). xylitol, sodium cyclamenate,
Included are saccharin and certain humectants such as sorbitol and mannitol. The fragrances used in the compositions of the present invention include sulfur compounds present in small amounts in natural mint oil, such as pul Bone, sabasin, etc.
(badine) and mercabutan. The buffer system included in the mouth rinse composition of the present invention is one that is capable of maintaining the pH of the composition in the desired range of about 4.0 to 5.6. In this pH range, the stability of the composition is very good, precipitation is avoided and the alkaloids are well incorporated into the plaque. Useful for the composition of the present invention! There are many i-series.

When no zinc salt is present in the composition, the Enokimachi system described below is useful. Sodium citrate/citric acid, sodium tartrate/sodium tartrate phosphate/sodium phosphate succinate/succinic acid! ? The following buffer system is useful when sodium Lvi/sodium lobionate/zinc brobionate salt is present in the composition. Sodium Citrate/Sodium Acetate Citrate/Sodium Acetate Tartrate/Tartaric Acid The present invention is further illustrated in the following examples.

Andhigetsu L A mouth rinse composition was prepared using the amounts listed in the table below.

It is important to add it to the LL% base (parts A and B). Examples of other specific buffer systems useful in the compositions of the invention are shown in the Examples and Tables below.

笾蚨IL fflL i生 LL%夾国 1L too. oo % To achieve optimal stability of the rinse composition, add a buffer system (part C) to the additive of Sanguinaria extract (part D) to avoid color changes and precipitate formation. Sodium Tartrate 0.60 1 . PluronicF-87, BASF
- Manufactured by Wyandotte is a polyoxyethylene, polyoxypropylene block polymer. 2. Tween 80, manufactured by ICI American, is a mixture of sorbitol oleate ester and anhydrous sorbitol, containing a large amount of monoester, and is condensed with about 20 moles of ethylene oxide.

The oral rinse described above is prepared as follows.

Add the ingredients of Part A to the main mixing vessel in the order listed, allowing the mixture to stand for 5 minutes between each addition and 15 minutes when all of Part A has been added. Add the ingredients of Part B to a separate mixing vessel in the order listed, allowing the mixture to stand for 5 minutes between each addition and 15 minutes when all of Part B has been added.
Dry mix Part C, add to main mixing vessel and mix for 15 minutes. To optimize the stability of the rinse, it is important to add the buffer in Part C to the rinse base before adding the Sanguinaria extract solution in Part D. Failure to follow this process will result in color changes and precipitation. Add Part D to the main mixing vessel, then add Part E to rinse the Part D vessel. After addition of Part E, the premixture is allowed to stand for 30 minutes and then passed through a filter with a normal pore size of 0.5 microns. Another example of a mouth rinse composition containing sanguinaria and zinc chloride is as follows. 100.00% To maintain a stable PH and a non-sedimenting rinse containing Sanguinaria in the absence of zinc, the formulation and 1 [systems are not limited to the above examples. Additional formulations in which zinc salts are not present are described below.

It has been found that adjusting the pH above 3 makes the Sanguinaria extract chemically more active and can react with impurities present in some excipients utilized in mouth rinses. For example, a mouth rinse composition that exhibits good chemical stability at pH 3.0 shows a significant reduction in sanguinarine content when the mouth rinse is adjusted to pH 4.5 to 5.5. The situation will be illustrated in the following example. 100.00
Examples of other additives that can be substituted for the citrate buffer in Part C are as follows.

Tartrate Buffer Acetate Buffer Phosphate Buffer Succinate Buffer 1L Salt Enokigai 1 Lobion Salt Buffer The mouth rinse described above is prepared using the same formulation as above.

Sanguinarine chloride (Sanguinarine ch.
When determining the reason for the loss of stability of Sanguinaria at high pH values (Loride), it was found that this decrease in stability at high pH values was partly due to the surfactant (Poloxamer 407). This finding was unexpected.6 This nonionic surfactant is a block copolymer of polyoxyethylene and polyoxybrobylene. The data below for oral rinses formulated at pH 6.0 show that as the concentration of Poloxamer in oral rinses increases, the stability of Sanguinaria decreases.

0.9 20P
oloxamer237 shows improved stability with a high pH formulation rinse, as shown in the data below.

237 5.2 9571
10 measurement results, po Ioxmer40
It was found that pol oxmer 237 had a higher level of unsaturation than pol oxmer 237, as shown in the table below. The degree of unsaturation is measured by reacting a methanol solution of mercury acetate with ρo I oxvier, adding sodium bromide, and then titrating the free acetic acid with a methanol solution of glacial potassium oxide. did. The clinical efficacy of Ehan Takumi Sanguinaria extract is based in part on its antibacterial activity. Sanguinarine is known to inhibit 98% of the microorganisms in tooth plaque. (Anti
Illicrobial Agent. s and C
hemoLtherapy, April 1985, 27:4
:663-665) The [C is generally less than 16 ppm for these microorganisms. It is also known that sanguinarine extracts are absorbed into the mouth and into soft and anti-inflammatory compositions.

(JADA Uo1, 108. March 1984, p33
g> It was found that increasing the pH of the oral rinse from 3.0 to 4.5-5.6 resulted in more sanguinarine and total benzophenanthridine alkaloids being incorporated into dental plaque, as shown in the data below. It was.

Uptake of sanguinarine and all benzophenanthridine alkaloids into moist plaque from oral rinses In addition to measuring the uptake of Sanguinaria extract into plaque, pH 3 and pH 4 were measured using a salivary glucose modification test method.
．． The efficacy of 5 rinses was also determined. Background: Initial saliva samples were collected and soaked in a test rinse for minutes. The purpose of the background saliva sample is to measure the shift of the sample in the next glucose test.After rinsing the subject saliva with a sanguinary rinse adjusted to pH 3.2 or 4.5, the sample should be placed under standard conditions. Refill again. Glucose was then added to the background and test saliva samples, and the mixture was incubated at 37°C for 3 hours. The pH of this mixture was measured at 5, 30, 60, 120, and 300 minutes. The degree of inhibition of salivary glycol degradation was determined by subtracting the background pH reading at each time point from the test pH reading at the corresponding time point. The PH of most background saliva samples decreased rapidly upon glucose addition.

That is, if rinsing provides a protective effect, the PH
The descent will be slower. Therefore, the greater the difference between the pH of the test substance and the pH of the background substance, the better the degree of inhibition of salivary glycol decomposition. The table below shows that treatment with a pH 4.5 rinse is more effective than treatment with a pH 3.2 rinse.

The number of objects was 7/n. Initial readings were used to adjust exogenous pH levels at each time point to determine differences between groups. Differences between test rinses were fully significant using analysis of variance (ANCOVA) with a P0.05 significance level. Inhibition of salivary glycol decomposition Addition of 5% glycol to baseline saliva After rinsing 1
Time spout 1L standing minute) pH 4.5 Rinse PH 3.2
Rinse l5 1.595 300 2.093 p}I=sample pH - background pH/each time point l 465 L626 1.720 1.523 1.055 ・, Rijin

Claims (1)

[Claims] 1. About 0.01 to 0.2% by weight of a benzophenanthridine alkaloid in an aqueous solution and a sufficient amount of buffer to adjust the pH of the composition to a range of 4.0 to 5.6. A stable oral rinse composition containing a system. 2. The alkaloid is sanguirin
narine), chelerythr.
ine), sanguilutine
, chelilutin, chelilubin (
chelirubine) and sangilbin (sang
2. The composition of claim 1, wherein the composition is selected from the group consisting of water-soluble salts of A. uilbine. 3. The buffer system described above is (a) sodium citrate and citric acid, (b) sodium acetate and acetic acid, (c) sodium tartrate and tartaric acid, (d) sodium phosphate and phosphoric acid, (
The composition of claim 1 selected from the group consisting of e) sodium succinate and succinic acid, (f) sodium lactate and lactic acid, and (g) sodium propionate and propionic acid. 4. The composition of claim 1 further comprising about 0.05 to 0.5% by weight of a water-soluble zinc salt. 5. The composition of claim 4, wherein said zinc salt is selected from the group consisting of zinc chloride, zinc acetate, zinc gluconate, zinc sulfate, zinc salicylate, zinc tartrate, zinc lactate, and zinc phenolsulfonate. 6. said buffer system is selected from the group consisting of (a) sodium citrate and citric acid, (b) sodium acetate and acetic acid, and (c) sodium tartrate and tartaric acid, and said zinc salt is zinc chloride. 6. The composition of claim 5. 7. Ethyl alcohol 5-25% by weight, wetting agent 2-15% by weight, surfactant 0.1-3% by weight, sweetener 0
．． 02 to 1% by weight and fragrance 0.05 to 0.4% by weight
the alkaloid is selected from the group consisting of sanguinarine and chelerythrine; and the composition has a pH of about 4.5. 8. About 0.01 to 0.2% by weight of a benzophenanthridine alkaloid in an aqueous solution, about 0.05 to 0.5% by weight of a zinc salt, and a pH of the composition in the range of 4.0 to 5.6. A stable mouth rinse composition containing a sufficient amount of a buffer system for conditioning. 9. said alkaloid is selected from the group consisting of sanguinarine, chelerythrine, sangiltin, chelirutin, cherirubine and sangilbin; and said buffer system comprises (a) sodium citrate and citric acid; (b) sodium acetate and acetic acid. and (c) sodium tartrate and tartaric acid. 10. The above zinc salt is water-soluble and contains 5 to 25% by weight of ethyl alcohol, 2 to 15% by weight of wetting agent, 0.1 to 3% by weight of surfactant, and 0.02 to 1% by weight of sweetener. The composition according to claim 8, further comprising 0.05 to 0.4% by weight of fragrance. 11. The composition of claim 9, wherein said zinc salt is zinc chloride and said alkaloid is selected from the group consisting of sanguinarine and chelerythrine.